PROJECT SUMMARY Diagnosing Sjgren's syndrome (SS) in the early stages of the disease can help mitigate damage from systemic manifestations that occur later in the disease. Current tests for establishing an SS diagnosis include salivary gland biopsy to look for lymphocytic inflammation and using radioactive labeling to test salivary gland function. While these tests are effective in the diagnosis of SS, the multiplex biosensor developed in this proposal will provide a low-cost method for detecting molecular evidence of both salivary/lacrimal gland hypofunction and lymphocytic inflammation without the need for invasive testing. Molecularly imprinted polymers (MIPs) are synthetic materials capable of semi-selective molecular recognition and are lower cost and more environmentally robust than antibodies. In this proposal, MIPs will be synthesized on the surface of nanomaterials with unique optical properties for use in sensing applications. Specifically, collections of MIP- coated gold nanomaterials will be employed in ?differential sensing,? routines to monitor biomarkers of lymphocytic inflammation and gland hypofunction simultaneously, providing a more comprehensive view of protein mixtures. Instead of identifying a single biomarker, the developed sensor arrays will generate a pattern based on numerous biomarkers, providing a more robust diagnostic tool for biochemical changes. The overall hypothesis of this proposal is that imprinted nanomaterials in optical sensor arrays may detect biomarkers that could be used to establish an SS diagnosis in symptomatic patients. The specific goals of this proposal are (Aim 1) to rationally choose strong-bonding monomers (non-covalent or reversible-covalent) to improve MIP affinity, (Aim 2) to synthesize MIPs on the surface of gold nanomateirals to generate receptors with built-in signal transduction and (Aim 3) to test these imprinted nanomaterials in sensor arrays to detect SS biomarkers.